AlcoholismPhase 2NCT01076283
A Study on the Biobehavioral Mechanisms of Baclofen and Alcohol Drinking
A Phase 2 study testing Baclofen and Cyproheptadine in people with Alcoholism, run by Brown University at 1 site in United States.
Trial summary
This pilot trial has the goal to demonstrate the feasibility of a study to test the effects of baclofen in a laboratory experiment using cue-reactivity and alcohol-self administration paradigms in non-treatment seeking alcohol-dependent subjects. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Alcoholism
- What is being tested?
- Baclofen and Cyproheptadine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to May 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- must be male or female between 21 and 65 years old (inclusive).
- participants must meet criteria for current Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) diagnosis of alcohol dependence, supported by the Structured Clinical Interview for DSM-IV-TR Axis I Disorders Patient Edition (SCID-I/P).
- participants must meet criteria for heavy drinking, defined as averaging ≥4 drinks/day for women and ≥5 drinks/day for men during a consecutive 30-day period within the 90 days prior to baseline evaluation (see: Anton et al, 2006). The gender-specific baseline was chosen as it represents heavy drinking that exceeds empirically based levels of moderate alcohol use that result in alcohol-related problems for women who consume ≥4 drinks/day, and men who consume ≥5 drinks/day (Sanchez-Craig et al, 1995).
- participants must be in good health as confirmed by medical history, physical examination, ECG, lab tests.
- females must be postmenopausal for at least one year, surgically sterile, or practicing an effective method of birth control before entry and throughout the study; have a negative urine pregnancy test at each visit.
- participants must be willing to take oral medication and adhere to the study procedures.
Who cannot join
- individuals expressing interest in treatment for alcoholism.
- pregnancy or breast feeding women or not using an adequate form of birth control
- positive urine drug screen at baseline for any illegal substance (a urine drug screen may be repeated once during the screening period).
- individuals diagnosed with a current substance dependence diagnosis, other than alcohol or nicotine.
- meet DSM-IV Axis I criteria for a lifetime diagnosis of schizophrenia, bipolar disorder, or other psychoses.
- an active illness within the past 6 months of Visit 1 that meet the DSM-IV criteria for a diagnosis of Major Depressive Disorder (MDD) or Anxiety Disorder. Subjects with a history of suicide will be excluded.
Show all 14Show fewer
- clinically significant medical abnormalities (i.e., unstable hypertension, ECG, bilirubin > 150% of the upper normal limit, ALT or AST elevations >300% the upper normal limit, creatinine clearance ≤ 60 dl/min).
- current use of psychotropic medications that cannot be discontinued that may have an effect on alcohol consumption or that may interact with baclofen or cyproheptadine.
- medical contraindications for use of baclofen or cyproheptadine.
- a history of adverse reaction or hypersensitivity to baclofen or cyproheptadine.
- individuals with a reasonable expectation of being institutionalized during the course of the trial.
- participants who have significant alcohol withdrawal symptoms, defined as a Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) >10.
- history of seizures (e.g. epilepsy).
- subjects who have participated in any behavioral and/or pharmacological study within the past 90 days.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brown University Center for Alcohol and Addiction Studies
Providence, Rhode Island, 02903
About this study
Official title: A Pilot Study on the Biobehavioral Mechanisms of Baclofen and Alcohol Drinking
This pilot trial has the goal to demonstrate the feasibility of a study to test the effects of baclofen in a laboratory experiment using cue-reactivity and alcohol-self administration paradigms in non-treatment seeking alcohol-dependent subjects.
- Conditions
- Alcoholism
- Being tested
- Baclofen, Cyproheptadine
- Keywords
- baclofen, alcoholism, urge, craving, alcohol drinking, biobehavioral mechanisms of baclofen in alcoholism
- Medical subject headings
- Alcoholism, Alcohol Drinking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BaclofenDrug
Baclofen 10mg t.i.d.
CyproheptadineDrug
'active' placebo
| Study group | Role | What they receive |
|---|---|---|
| Baclofen | Active comparator | Baclofen 10 mg three times a day (t.i.d.) for 8-10 days Receives: Drug: Baclofen |
| Cyproheptadine | Placebo comparator | Cyproheptadine 2 mg t.i.d. for 8-10 days Receives: Drug: Cyproheptadine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alcohol Urge
Whether baclofen, as compared to active placebo, results in diminished cue-reactivity responses to alcohol cues in terms of urge to drink [as measured by the Alcohol Urge Questionnaire (AUQ)] during the Cue Reactivity.
The Alcohol Urge Questionnaire (AUQ) consists of eight statements about the respondent's feelings and thoughts about drinking as they are completing the questionnaire (i.e., right now). The respondent is asked to respond to each statement about alcohol craving via a 7-item Likert scale ranging from "strongly disagree" to "strongly agree." Each item is scored on a 1 to 7 scale (Strongly Disagree = 1 and Strongly Agree = 7). Items 2 and 7 are reverse scored. A total score is computed by summing the item scores and ranges from 8 (lowest craving value) to 56 (highest craving value). Higher scores reflect greater craving (i.e. worse outcome).
Measured: approximately 8 days after drug administration
Alcohol Drinking
Whether baclofen, as compared to active placebo, results in lower quantity of alcohol consumed during the Alcohol Self-Administration (ASA).
Consistent with O'Malley et al. 2002, the ASA paradigm allows to use a fixed-dose (the priming drink), followed by a 2-hour "free-choice" phase when subjects may choose to drink or not up to 8 mini-drinks. Participants receive a monetary compensation of $3 dollars per each mini-drink not consumed; therefore the amount of minidrinks consumed during the 2-hour sessions ranges 0-8, and the monetary compensation ranges $0-24. The quantity of alcohol consumed during the free-choice session is expressed as "standard drinking unit", where a standard drink unit contains about 14 grams of pure alcohol (about 0.6 fluid ounces or 1.2 tablespoons).
Measured: approximately 8 days after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2010 (estimated)
- Study startDec 2009
- Primary completionApr 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for AlcoholismStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lorenzo Leggio, Brown University
- Investigators
- Lorenzo Leggio, M.D., M.Sc., Principal investigator, Brown University Center for Alcohol and Addiction Studies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01076283
- Sponsor's protocol ID
- 0906000002
- Status last verified
- Oct 2013
- First submitted
- 25 Feb 2010
- Last updated
- 17 Oct 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Leggio L, Garbutt JC, Addolorato G. Effectiveness and safety of baclofen in the treatment of alcohol dependent patients. CNS Neurol Disord Drug Targets. 2010 Mar;9(1):33-44. doi: 10.2174/187152710790966614.
PubMed 20201813Evans SM, Bisaga A. Acute interaction of baclofen in combination with alcohol in heavy social drinkers. Alcohol Clin Exp Res. 2009 Jan;33(1):19-30. doi: 10.1111/j.1530-0277.2008.00805.x. Epub 2008 Oct 6.
PubMed 18840257Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, Abenavoli L, D'Angelo C, Caputo F, Zambon A, Haber PS, Gasbarrini G. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet. 2007 Dec 8;370(9603):1915-22. doi: 10.1016/S0140-6736(07)61814-5.
PubMed 18068515Addolorato G, Leggio L, Abenavoli L, Agabio R, Caputo F, Capristo E, Colombo G, Gessa GL, Gasbarrini G. Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam. Am J Med. 2006 Mar;119(3):276.e13-8. doi: 10.1016/j.amjmed.2005.08.042.
PubMed 16490478Addolorato G, Leggio L, Abenavoli L, DeLorenzi G, Parente A, Caputo F, Janiri L, Capristo E, Rapaccini GL, Gasbarrini G. Suppression of alcohol delirium tremens by baclofen administration: a case report. Clin Neuropharmacol. 2003 Sep-Oct;26(5):258-62. doi: 10.1097/00002826-200309000-00010.
PubMed 14520166Addolorato G, Leggio L, Abenavoli L, Caputo F, Gasbarrini G. Tolerance to baclofen's sedative effect in alcohol-addicted patients: no dissipation after a period of abstinence. Psychopharmacology (Berl). 2005 Mar;178(2-3):351-2. doi: 10.1007/s00213-004-2014-4. Epub 2004 Sep 30. No abstract available.
PubMed 15719231Colombo G, Addolorato G, Agabio R, Carai MA, Pibiri F, Serra S, Vacca G, Gessa GL. Role of GABA(B) receptor in alcohol dependence: reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics. Neurotox Res. 2004;6(5):403-14. doi: 10.1007/BF03033315.
PubMed 15545024Addolorato G, Caputo F, Capristo E, Domenicali M, Bernardi M, Janiri L, Agabio R, Colombo G, Gessa GL, Gasbarrini G. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol. 2002 Sep-Oct;37(5):504-8. doi: 10.1093/alcalc/37.5.504.
PubMed 12217947Leggio L, Zywiak WH, McGeary JE, Edwards S, Fricchione SR, Shoaff JR, Addolorato G, Swift RM, Kenna GA. A human laboratory pilot study with baclofen in alcoholic individuals. Pharmacol Biochem Behav. 2013 Feb;103(4):784-91. doi: 10.1016/j.pbb.2012.11.013. Epub 2012 Dec 19.
PubMed 23262301
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study on the Biobehavioral Mechanisms of Baclofen and Alcohol Drinking
- ClinicalTrials.gov ID
- NCT01076283
- Acronym / sponsor ID
- 0906000002
- Conditions
- Alcoholism
- Keywords
- baclofen, alcoholism, urge, craving, alcohol drinking, biobehavioral mechanisms of baclofen in alcoholism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Apr 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 26 Feb 2010 (estimated)
- Results
- Posted 17 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot trial has the goal to demonstrate the feasibility of a study to test the effects of baclofen in a laboratory experiment using cue-reactivity and alcohol-self administration paradigms in non-treatment seeking alcohol-dependent subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Baclofen | Active comparator | Drug: BaclofenBaclofen 10 mg three times a day (t.i.d.) for 8-10 days |
| Cyproheptadine | Placebo comparator | Drug: CyproheptadineCyproheptadine 2 mg t.i.d. for 8-10 days |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- must be male or female between 21 and 65 years old (inclusive).
- participants must meet criteria for current Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) diagnosis of alcohol dependence, supported by the Structured Clinical Interview for DSM-IV-TR Axis I Disorders Patient Edition (SCID-I/P).
- participants must meet criteria for heavy drinking, defined as averaging ≥4 drinks/day for women and ≥5 drinks/day for men during a consecutive 30-day period within the 90 days prior to baseline evaluation (see: Anton et al, 2006). The gender-specific baseline was chosen as it represents heavy drinking that exceeds empirically based levels of moderate alcohol use that result in alcohol-related problems for women who consume ≥4 drinks/day, and men who consume ≥5 drinks/day (Sanchez-Craig et al, 1995).
- participants must be in good health as confirmed by medical history, physical examination, ECG, lab tests.
- females must be postmenopausal for at least one year, surgically sterile, or practicing an effective method of birth control before entry and throughout the study; have a negative urine pregnancy test at each visit.
Key exclusion criteria (14 listed)
- individuals expressing interest in treatment for alcoholism.
- pregnancy or breast feeding women or not using an adequate form of birth control
- positive urine drug screen at baseline for any illegal substance (a urine drug screen may be repeated once during the screening period).
- individuals diagnosed with a current substance dependence diagnosis, other than alcohol or nicotine.
- meet DSM-IV Axis I criteria for a lifetime diagnosis of schizophrenia, bipolar disorder, or other psychoses.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BaclofenBaclofen 10mg t.i.d. | Drug | Baclofen |
| Cyproheptadine'active' placebo | Drug | Cyproheptadine |
Primary outcome
Alcohol Urge
Time frame: approximately 8 days after drug administration
Whether baclofen, as compared to active placebo, results in diminished cue-reactivity responses to alcohol cues in terms of urge to drink [as measured by the Alcohol Urge Questionnaire (AUQ)] during the Cue Reactivity. The Alcohol Urge Questionnaire (AUQ) consists of eight statements about the respondent's feelings and thoughts about drinking as they are completing the questionnaire (i.e., right now). The respondent is asked to respond to each statement about alcohol craving via a 7-item Likert scale ranging from "strongly disagree" to "strongly agree." Each item is scored on a 1 to 7 scale (Strongly Disagree = 1 and Strongly Agree = 7). Items 2 and 7 are reverse scored. A total score is computed by summing the item scores and ranges from 8 (lowest craving value) to 56 (highest craving value). Higher scores reflect greater craving (i.e. worse outcome).
Alcohol Drinking
Time frame: approximately 8 days after drug administration
Whether baclofen, as compared to active placebo, results in lower quantity of alcohol consumed during the Alcohol Self-Administration (ASA). Consistent with O'Malley et al. 2002, the ASA paradigm allows to use a fixed-dose (the priming drink), followed by a 2-hour "free-choice" phase when subjects may choose to drink or not up to 8 mini-drinks. Participants receive a monetary compensation of $3 dollars per each mini-drink not consumed; therefore the amount of minidrinks consumed during the 2-hour sessions ranges 0-8, and the monetary compensation ranges $0-24. The quantity of alcohol consumed during the free-choice session is expressed as "standard drinking unit", where a standard drink unit contains about 14 grams of pure alcohol (about 0.6 fluid ounces or 1.2 tablespoons).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20201813Leggio L, Garbutt JC, Addolorato G. Effectiveness and safety of baclofen in the treatment of alcohol dependent patients. CNS Neurol Disord Drug Targets. 2010 Mar;9(1):33-44. doi: 10.2174/187152710790966614.
- Background: PubMed 18840257Evans SM, Bisaga A. Acute interaction of baclofen in combination with alcohol in heavy social drinkers. Alcohol Clin Exp Res. 2009 Jan;33(1):19-30. doi: 10.1111/j.1530-0277.2008.00805.x. Epub 2008 Oct 6.
- Background: PubMed 18068515Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, Abenavoli L, D'Angelo C, Caputo F, Zambon A, Haber PS, Gasbarrini G. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet. 2007 Dec 8;370(9603):1915-22. doi: 10.1016/S0140-6736(07)61814-5.
- Background: PubMed 16490478Addolorato G, Leggio L, Abenavoli L, Agabio R, Caputo F, Capristo E, Colombo G, Gessa GL, Gasbarrini G. Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam. Am J Med. 2006 Mar;119(3):276.e13-8. doi: 10.1016/j.amjmed.2005.08.042.
- Background: PubMed 14520166Addolorato G, Leggio L, Abenavoli L, DeLorenzi G, Parente A, Caputo F, Janiri L, Capristo E, Rapaccini GL, Gasbarrini G. Suppression of alcohol delirium tremens by baclofen administration: a case report. Clin Neuropharmacol. 2003 Sep-Oct;26(5):258-62. doi: 10.1097/00002826-200309000-00010.
- Background: PubMed 15719231Addolorato G, Leggio L, Abenavoli L, Caputo F, Gasbarrini G. Tolerance to baclofen's sedative effect in alcohol-addicted patients: no dissipation after a period of abstinence. Psychopharmacology (Berl). 2005 Mar;178(2-3):351-2. doi: 10.1007/s00213-004-2014-4. Epub 2004 Sep 30. No abstract available.
- Background: PubMed 15545024Colombo G, Addolorato G, Agabio R, Carai MA, Pibiri F, Serra S, Vacca G, Gessa GL. Role of GABA(B) receptor in alcohol dependence: reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics. Neurotox Res. 2004;6(5):403-14. doi: 10.1007/BF03033315.
- Background: PubMed 12217947Addolorato G, Caputo F, Capristo E, Domenicali M, Bernardi M, Janiri L, Agabio R, Colombo G, Gessa GL, Gasbarrini G. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol. 2002 Sep-Oct;37(5):504-8. doi: 10.1093/alcalc/37.5.504.
- Results publication: PubMed 23262301Leggio L, Zywiak WH, McGeary JE, Edwards S, Fricchione SR, Shoaff JR, Addolorato G, Swift RM, Kenna GA. A human laboratory pilot study with baclofen in alcoholic individuals. Pharmacol Biochem Behav. 2013 Feb;103(4):784-91. doi: 10.1016/j.pbb.2012.11.013. Epub 2012 Dec 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorenzo Leggio, M.D., M.Sc. principal investigator
Brown University Center for Alcohol and Addiction Studies
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Baclofen and Cyproheptadine in people with Alcoholism, run by Brown University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alcohol Urge (time frame: approximately 8 days after drug administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01076283, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2013.